1. Field of the Invention
This invention relates to semiconductor materials and methods of preparation and, more particularly, to amperometric receptor-based sensors.
2. Description of the Prior Art
Sensor devices which use receptor molecules for chemical detection are based primarily on two schemes: amperometric and capacitive. An amperometric scheme most closely mimics the physiological functions of the receptor molecules.
In the prior art such as Jarvis, Biosensors: Today's Technology, Tomorrow's Products pp.155, SEAI Technical Publications, Madison, Ga., 1986, or Turner et al., Biosensors: Fundamentals and Applications, p. 770, Oxford University Press, New York, N.Y., 1987, a lipid bilayer is deposited onto a porous, hydrophilic film, which, in turn, is deposited onto a support electrode. Ligand-activated ion channels or voltage-gated ion channels are co-deposited with the lipid membrane, or inserted after the lipid membrane has been deposited. The support electrode and a reference electrode are placed in an electrolyte bath of fixed pH or a known ionic strength When a channel is excited by a stimulus in this bath, an ion current flows through the excited channel from the reference electrode to the support electrode. This is also discussed in Yager, United States SIR No. H201, issued Jan. 6, 1987.
In these type of prior art devices it is essential that the lipid membrane serves as a highly impermeable seal against the free flow of the ions from one electrode to the other (the background current, part of the noise in the measurement), or else the ion current through the receptor is drowned out in the background current. A good seal can be measured as a high (electrical) impedance for current flow.
As taught by Arya et al. "Langmuir-Blodgett Deposition of Lipid Films on Hydrogel as a Basis for Biosensor Development," Anal. Chim. Acta 173: 331-336, 1985, and Thompson et al., "The Structure and Electrochemical Properties of a Polymer Supported Lipid Biosensor," Anal. Chim. Acta 117: 133-155, 1980, the usual configuration of the amperometric electrode consists of a silver-silver chloride wire or thin film upon which a thin layer of a hydrophilic, porouspolymer (such as polyhydroxyethylmethacrylate, PHEMA) has been deposited. A lipid bilayer is deposited either by a Langmuir-Blodgett dipping technique, or by brushing on a mixture of lipids and solvent onto the polymer, and allowing the bilayer to thin on the electrode (similar to the technique developed for black lipid membranes, BLM's).
These techniques suffer from several deficiencies: first, there is some difficulty getting the polymer to adhere to the silver-silver chloride; second, there is a problem with getting the lipids to adhere to the polymer to give a high impedance seal, which, in turn, contributes to the noise of the measurement; third, it is inherently difficult to remove some of the background noise because of the large area of these electrodes.
Efforts have been made to reduce the area of these devices, but these efforts have been limited by the art's ability to control the deposition of the polymer. The primary drawback caused by this problem is an inability to control the background current contribution to the circuit noise.
The second approach, the capacitive technique, has been developed for use with a non-porous substrate upon which two electrodes in the form of interdigitated metallic fingers have been deposited. This approach is described in articles by M. Eldefrawi et al.,"Acetylcholine Receptor-Based Biosensor", Third Annual Conference on Receptor-Based Biosensors, Laurel, Md. Sep. 11-12, 1987, and A. L. Newman et al., "Advances in Capacitive Affinity Sensor Technology", Third Annual Conference on Receptor-Based Biosensors, Laurel, Md., Sep. 11-12, 1987.
The lipid-protein films are deposited on top of the metallic fingers. The substrate is placed in a reference bath, and the A.C. impedance of the films is measured either between the fingers of the two deposited electrodes, or between a reference electrode and one of the finger electrodes. The main drawback to this technique is that it suffers from a lack of sensitivity. The measurement does not offer any inherent advantage for amplifying the signal without introducing a similar amplification of the background noise.
The problem with both of these techniques is that if one wishes to increase the signal from the receptors, either one increases the surface area of the device or one increases the number of receptors per unit area. If the concentration of the receptor molecules is limited, then one would like to fabricate a device which will give the largest signal per receptor concentration.
One way to increase the signal is to make the devices larger; however, an increase in the surface area of these devices also results in an increase in the noise contribution, which may not be filtered out of the signal. In addition, it is desirable to make these devices as small as possible to avoid defects in the thin lipid bilayer. One would ultimately like to increase the receptor signal without increasing the noise (also called increasing the signal-to-noise ratio, SNR) and to do this for the smallest area possible.
In U.S. Pat. No. 4,562,157, Lowe et al. describes a sensor in which two or more biochemical species are positioned on the surface of an FET transistor. The biochemical material is essentially printed on the surface of the FET by lithographic means. The device works by measuring capacitance.
Burkhardt et al., in U.S. Pat. Nos. 4,144,636 and 4,057,832, describes a sensor which utilizes a porous silicon layer protected by an oxide layer on a silicon dioxide base. The device can only measure humidity.
These prior art devices are not shown as sensitive sensors capable of detecting a broad range of reactive entities while maintaining a low signal to noise ratio.